Erythropoietin is a natural glycoprotein hormone produced predominantly by the peritubular interstitial cells in the kidney, and transported via the blood to the bone marrow, where it regulates and promotes the maturation of erythroid cells into mature red blood cells. Fibroblast-like cells in the cortical interstitium of the kidney synthesize erythropoietin while tubular cells do not. The former specialized cells express 5′-nucleotidase or CD73 on their surface and are strategically located so as to facilitate erythropoietin secretion into peritubular capillaries, which, in turn, carry erythropoietin past most nephron segments, into the systemic circulation. Significantly, erythropoietin producing cells are in direct contact with the basolateral aspects of proximal tubular and outer medullary cells. This anatomic relationship facilitates bidirectional signaling between tubular and fibroblast-like cells. This is exemplified by paracrine erythropoietin signaling in erythropoietin-receptor-expressing adjacent tubular cells, where signals that originate in proximal tubular cells affect the function of adjacent peritubular fibroblast-like cells.
Decreased production of erythropoietin results in fewer circulating red blood cells or anemia, often associated with end stage renal disease, malignancies, HIV infection and AIDS, rheumatoid arthritis, myeloma and myeloplastic syndrome as well as other diseases and disorders. Currently, the only therapeutic option for erythropoietin-responsive anemia or disorders is the administration of recombinant human erythropoietin (rHuEpo). Disclosed are compositions and methods for the production of erythropoietin.